In the following discussion certain articles and methods will be described for background and introductory purposes. Nothing contained herein is to be construed as an “admission” of prior art. Applicant expressly reserves the right to demonstrate, where appropriate, that the articles and methods referenced herein do not constitute prior art under the applicable statutory provisions.
Accumulation of the α-synuclein protein has been associated with several neurodegenerative diseases, termed synucleinopathies. These diseases share the same feature, insoluble inclusions in the neurons and the glia of the brain called Lewy bodies which are composed primarily of α-synuclein. Lewy bodies and Lewy neurites are the neuropathological hallmarks Parkinson's disease (PD) and other diseases including diffuse Lewy body disease (DLBD), Lewy body variant of Alzheimer's disease (LBVAD), combined PD and Alzheimer's disease (AD), multiple systems atrophy (MSA) and Dementia with Lewy bodies (DLB).
AD, PD, MSA and DLB are the most common neurodegenerative disorders in the elderly. Although each neurodegenerative disease appears to have a predilection for specific brain regions and cell populations, resulting in distinct pathological features, PD, AD, MSA, DLB and LBD also share common pathological hallmarks. Subjects with familial AD, Down syndrome, or sporadic AD develop LBs on the amygdala, which are the classical neuropathological hallmarks of PD. Additionally, each disease is associated with the degeneration of neurons, interneuronal synaptic connections and eventually cell death, the depletion of neurotransmitters, and abnormal accumulation of misfolded proteins, the precursors of which participate in normal central nervous system function. Biochemical studies have confirmed the link between AD, PD, MSA and DLB.
The present invention is directed to treatment of PD and other synucleinopathies associated with Lewy bodies by administration of therapeutic antibodies that selectively bind to an epitope of α-synuclein to a subject under conditions that generate a beneficial response in the subject. The invention addresses a significant clinically unmet need for therapeutic regimes for preventing or ameliorating the neuropathology and cognitive impairment associated with PD and other diseases associated with Lewy bodies.